miRNAs reshape immunity and inflammatory responses in bacterial infection

Zhou, Xikun; Li, Xuefeng; Wu, Min

doi:10.1038/s41392-018-0006-9

Cited by 113 publications

(115 citation statements)

References 169 publications

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“…Recent studies have associated the expression levels of several miRNAs with fundamental cellular processes such as cell apoptosis, phagocytosis, inflammation and macrophage polarization upon bacterial infection (20,47). The present study demonstrated that expression levels of miR-142-5p and miR-146a-5p are negatively regulated by SFN, suggesting their involvement in SFN-mediated decrease of cell apoptosis.…”

supporting

confidence: 60%

“…Post-transcriptional regulation by microRNAs (miRNAs) has emerged as a major regulatory mechanism to control the expression level of genes involved in a number of fundamental cellular processes such as inflammation, proliferation, apoptosis and macrophage polarization upon pathogenic infection (20). miRNAs are molecules measuring 18-24 nucleotides in length and belong to the short non-coding RNA family.…”

Section: Introductionmentioning

confidence: 99%

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Sulforaphane reduces intracellular survival of Staphylococcus aureus in macrophages through inhibition of JNK and p38 MAPK‑induced inflammation

Deramaudt¹,

Ali²,

Vinit³

et al. 2020

Int J Mol Med

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Macrophages are active contributors to the innate immune defense system. As macrophage activation is clearly affected by the surrounding microenvironment, the present study investigated the effect of sulforaphane (SFN) on the bactericidal activity of macrophages and the underlying molecular mechanisms involved in this process. Human THP-1-derived macrophages, primary human peripheral blood mononuclear cell-derived macrophages, and primary mouse bone marrow derived-macrophages (BMdMs) pretreated with SFN or dMSO were utilized in a model of Staphylococcus aureus infection. The results suggested that SFN pretreatment of macrophages effectively repressed the intracellular survival of S. aureus through modulation of p38/JNK signaling and decreased S. aureus-induced caspases-3/7-dependent cell apoptosis, potentially through downregulation of microRNA (miR)-142-5p and miR-146a-5p. As SFN is a well-known activator of nuclear factor erythroid 2-related factor 2 (Nrf2), Nrf2 -/-BMdMs were used to demonstrate that the SFN-mediated inhibitory effect was independent of Nrf2. Nevertheless, an increase in intracellular bacterial survival in Nrf2-deficient macrophages was observed. In addition, SFN pretreatment suppressed S. aureus-induced transcriptional expression of genes coding for the proinflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), as well as for the M1 markers c-c motif chemokine receptor 7, IL-23 and inducible nitric oxide synthase (iNOS). Western blot analysis indicated that S. aureus challenge activated p38 mitogen-activated protein kinase (MAPK) (p38) and c-Jun N-terminal kinase (JNK) MAPK signaling pathways, while SFN pretreatment prevented p38 and JNK phosphorylation. Pretreatment with 2 specific inhibitors of p38 and JNK, SB203580 and SP600125, respectively, resulted in a decrease in S. aureus-induced proinflammatory gene expression levels compared with those observed in the SFN-pretreated macrophages. Furthermore, THP-1-derived macrophages pretreated with SB203580 or SP600125 prior to bacterial infection exhibited a significant inhibition in intracellular S. aureus survival.In conclusion, we hypothesize that concomitant targeting of the p38/JNK-inflammatory response and the S. aureus-induced apoptosis with SFN may be a promising therapeutic approach in S. aureus infection.

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supporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Sulforaphane reduces intracellular survival of Staphylococcus aureus in macrophages through inhibition of JNK and p38 MAPK‑induced inflammation

Deramaudt¹,

Ali²,

Vinit³

et al. 2020

Int J Mol Med

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“…Cells total ROS produced in the cultured cells were stained with DCFH‐DA. After t‐BHP treatment, DCFH‐DA at a final concentration of 10 µM in diluted in DMEM was added at 37°C for 30 min in the dark (X. Zhou, Li, & Wu, ). The fluorescence was then measured with flow cytometry and fluorescence microscopy (L. Zhou, Zhang, Davies, & Forman, ).…”

Section: Methodsmentioning

confidence: 99%

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

Wang

Zhao

et al. 2019

Journal Cellular Physiology

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Atherosclerosis (AS) is a major pathogenic factor in patients with cardiovascular diseases, and endothelial dysfunction (ED) plays a primary role in the occurrence and development of AS. In our study, we attempted to evaluate the role of phosphatase and tensin homolog (PTEN) in endothelial cell apoptosis under oxidized low-density lipoprotein (ox-LDL) stimulation and identify the associated mechanisms. The results of our study demonstrated that ox-LDL induced human umbilical vein endothelial cell (HUVEC) death via mitochondrial apoptosis, as evidenced by reduced mitochondrial potential, increased mitochondria permeability transition pore opening, cellular calcium overload, and caspase-9/-3 activation. In addition, ox-LDL also suppressed cellular energy production via downregulating the mitochondrial respiratory complex. Moreover, ox-LDL impaired HUVECs migration. Western blot analysis showed that PTEN expression was upregulated after exposure to ox-LDL and knockdown of PTEN could attenuate ox-LDL-mediated endothelial cell damage. Furthermore, we found that ox-LDL impaired mitophagy activity, whereas PTEN deletion could improve mitophagic flux and this effect relied on the activity of the AMPactivated protein kinase (AMPK)-cAMP-response element-binding protein (CREB)-Mitofusin-2 (Mfn2) axis. When the AMPK-CREB-Mfn2 pathway was inhibited, PTEN deletion-associated HUVECs protection was significantly reduced, suggesting that the AMPK-CREB-Mfn2-mitophagy axis is required for PTEN deletion-mediated endothelial cell survival under ox-LDL. Taken together, our results indicate that ox-LDL-induced endothelial cell damage is associated with PTEN overexpression, and inhibition of PTEN could promote endothelial survival via activating the AMPK-CREB-Mfn2-mitophagy signaling pathway. K E Y W O R D S AMPK-CREB-Mfn2 signaling pathway, endothelial cell dysfunction, Mfn2, mitophagy, ox-LDL, PTEN

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“…miR-155 is another important regulator of the inflammatory response, with recent studies highlighting its key role during bacterial infection, where it acts as a negative regulator of inflammation [235]. Bandyopadhyay et al showed that the inducing of miR-155 during Francisella tularensis infection prompted the translational repression of MyD88 and SHIP-1, thus inhibiting the secretion of endotoxin-stimulated TNFα and attenuating the innate inflammatory response [236].…”

Section: Mirnas In Sepsismentioning

confidence: 99%

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

Condrat

Thompson

Barbu

et al. 2020

Cells

843

583

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MicroRNAs (miRNAs) represent a class of small, non-coding RNAs with the main roles of regulating mRNA through its degradation and adjusting protein levels. In recent years, extraordinary progress has been made in terms of identifying the origin and exact functions of miRNA, focusing on their potential use in both the research and the clinical field. This review aims at improving the current understanding of these molecules and their applicability in the medical field. A thorough analysis of the literature consulting resources available in online databases such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate was performed. There is promising evidence that in spite of the lack of standardized protocols regarding the use of miRNAs in current clinical practice, they constitute a reliable tool for future use. These molecules meet most of the required criteria for being an ideal biomarker, such as accessibility, high specificity, and sensitivity. Despite present limitations, miRNAs as biomarkers for various conditions remain an impressive research field. As current techniques evolve, we anticipate that miRNAs will become a routine approach in the development of personalized patient profiles, thus permitting more specific therapeutic interventions.Biogenesis of miRNA begins in the nucleus, where the transcription of its precursor, primary miRNA or pri-miRNA takes place under the influence of RNA polymerases II and III [11,12]. The resulting molecule is a hairpin-like structure, which contains a loop at one end [11]. This primordial mi-RNA precursor that is usually made up of hundreds of nucleotides is then processed consecutively by two RNase III enzymes [13][14][15]. The first enzyme to act upon the pri-miRNA, which still resides in the nucleus, is called Drosha or DCGR8, and turns it into a new hairpin-like structure of approximately 70 nucleotides, the Precursor-miRNA or pre-miRNA. The latter is then transported to the cytoplasm, with the help of Exportin-5, where it is cleaved again by the Ago2/Dicer complex leading to the short, mature miRNA double strands [16].Further on, one of the strands, usually known as the guide strand, will be integrated into the RNA-induced silencing complex (RISC), while the other one, known as the passenger strand, is going to be degraded, even though in some occasions it has been found to be also functional [17]. In most cases, the strand that contains the less stable 5 end or a uracil at the beginning is more likely to be selected as the guide strand [18][19][20]. In those situations, where the passenger strand is not degraded and both get incorporated into the miRISC complex, the mature miRNA in the guide strand will be the dominant one [21,22].The main role of miRNA in the human body is gene regulation [23] by mediating the degradation of mRNA and also by regulating transcription and translation through canonical and non-canonical mechanisms [4]. The canonical mechanism means that the miRISC complex containing the miRNA guide strand is exerting its action by binding to the targ...

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miRNAs reshape immunity and inflammatory responses in bacterial infection

Cited by 113 publications

References 169 publications

Sulforaphane reduces intracellular survival of Staphylococcus aureus in macrophages through inhibition of JNK and p38 MAPK‑induced inflammation

Sulforaphane reduces intracellular survival of Staphylococcus aureus in macrophages through inhibition of JNK and p38 MAPK‑induced inflammation

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

miRNAs as Biomarkers in Disease: Latest Findings Regarding Their Role in Diagnosis and Prognosis

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